Our proposed experiments encompass in vivo and in vitro studies of the synthesis and actions of neuronotrophic factors in the NGF and FGF hybridization of mRNA or immunocytochemistry of the protein product, in which brain region each of these factors is synthesized ad whether there are changes during senescence. The in vitro studies will include the development of systems to produce useable amounts of growth factors and which can also be transplanted into the brain. We will used such transplants, as well as other means of administration, to determine if the factors can rescue neurons from degeneration during aging. Although neuronotrophic factors have only recently been characterized as important for neuron survival in the adult brain, they would seem to be promising mechanisms for the study of aging in humans. The possibility of one or more factors evolving into therapeutic agents has been raised. While premature human experimentation should be avoided, it would be useful to have initial information about the relevance of these biological mechanisms in human aging, to guide the basic science work. In the rear, we will also study these growth factors in brain tissue obtained from human subjects,l including young and aged subjects, and patients with Alzheimer's Disease. Our laboratory has obtain favorable results with infusion of NGF, together with transplantation of adrenal medullary tissue, into the basal ganglia of a patient with Parkinsons's disease. Because this NGF infusion did not harm the patient and may have had a beneficial effect, we propose a pilot exploration of the effects of NGF in patients with Alzheimer's disease.